Alopecia areata is characterised by non-scarring loss of scalp, face, or body hair. We investigated the efficacy and safety of ritlecitinib, an oral, selective dual JAK3/TEC family kinase inhibitor, in patients with alopecia areata. In this randomised, double-blind, multicentre, phase 2b–3 trial done at 118 sites in 18 countries, patients aged 12 years and older with alopecia areata and at least 50% scalp hair loss were randomly assigned to oral ritlecitinib or placebo once-daily for 24 weeks, with or without a 4-week loading dose (50 mg, 30 mg, 10 mg, 200 mg loading dose followed by 50 mg, or 200 mg loading dose followed by 30 mg), followed by a 24-week extension period during which ritlecitinib groups continued their assigned doses and patients initially assigned to placebo switched to ritlecitinib 50 mg or 200 mg loading dose followed by 50 mg. Randomisation was done by use of an interactive response system and was stratified by baseline disease severity and age. The sponsor, patients, and investigators were masked to treatment, and all patients received the same number of tablets to maintain masking. The primary endpoint was Severity of Alopecia Tool (SALT) score 20 or less at week 24. The primary endpoint was assessed in all assigned patients, regardless of whether they received treatment. This study was registered with , . Between Dec 3, 2018, and June 24, 2021, 1097 patients were screened and 718 were randomly assigned to receive ritlecitinib 200 mg + 50 mg (n=132), 200 mg + 30 mg (n=130), 50 mg (n=130), 30 mg (n=132), 10 mg (n=63), placebo to 50 mg (n=66), or placebo to 200 mg + 50 mg (n=65). 446 (62%) of 718 patients were female and 272 (38%) were male. 488 (68%) were White, 186 (26%) were Asian, and 27 (4%) were Black or African American. Of 718 patients randomly assigned, 104 patients discontinued treatment (34 withdrew, 19 adverse events [AEs], 12 physician decision, 12 lack of efficacy, 13 lost to follow up, five rolled over to long-term study transfer, four pregnancies, two protocol deviations, one declined to attend follow-up due to COVID-19, one attended last visit very late due to COVID-19, and one non-compliance). At week 24, 38 (31%) of 124 patients in the ritlecitinib 200 mg + 50 mg group, 27 (22%) of 121 patients in the 200 mg + 30 mg group, 29 (23%) of 124 patients in the 50 mg group, 17 (14%) of 119 patients in the 30 mg group, and two (2%) of 130 patients in the placebo group had a response based on SALT score 20 or less. The difference in response rate based on SALT score 20 or less between the placebo and the ritlecitinib 200 mg + 50 mg group was 29·1% (95% CI 21·2–37·9; p<0·0001), 20·8% (13·7–29·2; p<0·0001) for the 200 mg + 30 mg group, 21·9% (14·7–30·2; p<0·0001) for the 50 mg group, and 12·8% (6·7–20·4; p=0·0002) for the 30 mg group. Up to week 48 and including the follow-up period, AEs had been reported in 108 (82%) of 131 patients in the ritlecitinib 200 mg + 50 mg group, 105 (81%) of 129 patients in the 200 mg + 30 mg group, 110 (85%) of 130 patients in the 50 mg group, 106 (80%) of 132 patients in the 30 mg group, 47 (76%) of 62 patients in the 10 mg group, 54 (83%) of 65 patients placebo to ritlecitinib 200 mg + 50 mg in the extension period, and 57 (86%) of 66 patients in the placebo to 50 mg group. The incidence of each AE was similar between groups, and there were no deaths. Ritlecitinib was effective and well tolerated in patients aged 12 years and older with alopecia areata. Ritlecitinib might be a suitable treatment option for alopecia areata in patients who are candidates for systemic therapy. Pfizer.

中文翻译：

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Ritlecitinib 对成人和青少年斑秃的疗效和安全性：一项随机、双盲、多中心、2b-3 期试验

斑秃的特征是头皮、面部或体毛的非疤痕性脱落。我们研究了 Ritlecitinib（一种口服选择性双 JAK3/TEC 家族激酶抑制剂）对斑秃患者的疗效和安全性。在这项随机、双盲、多中心、2b-3 期试验中，在 18 个国家的 118 个地点进行，12 岁及以上患有斑秃和至少 50% 头皮脱发的患者被随机分配至口服 Ritlecitinib 或安慰剂组。每日一次，持续 24 周，有或没有 4 周负荷剂量（50 mg、30 mg、10 mg、200 mg 负荷剂量，随后 50 mg，或 200 mg 负荷剂量，随后 30 mg），然后是 24 周延长期，在此期间，ritlecitinib 组继续分配剂量，最初分配安慰剂的患者改为 ritlecitinib 50 mg 或 200 mg 负荷剂量，然后是 50 mg。随机化是通过使用交互式响应系统进行的，并根据基线疾病严重程度和年龄进行分层。申办者、患者和研究者均对治疗进行掩蔽，所有患者均接受相同数量的药片以维持掩蔽。主要终点是第 24 周时脱发严重程度工具 (SALT) 评分为 20 或更低。主要终点在所有分配的患者中进行评估，无论他们是否接受治疗。这项研究已在 注册。2018年12月3日至2021年6月24日期间，筛选了1097名患者，其中718名患者被随机分配接受ritlecitinib 200 mg + 50 mg (n=132)、200 mg + 30 mg (n=130)、50 mg (n=130) =130)、30 mg (n=132)、10 mg (n=63)、安慰剂至 50 mg (n=66) 或安慰剂至 200 mg + 50 mg (n=65)。718 名患者中有 446 名 (62%) 为女性，272 名 (38%) 为男性。488 人（68%）是白人，186 人（26%）是亚裔，27 人（4%）是黑人或非裔美国人。在随机分配的 718 名患者中，104 名患者停止治疗（34 名退出，19 名不良事件 [AE]，12 名医生决定，12 名缺乏疗效，13 名失访，5 名转入长期研究转移，4 名怀孕，2 名方案偏差，一名因 COVID-19 拒绝参加随访，一名因 COVID-19 很晚才参加最后一次就诊，一名不遵守规定）。第24周时，ritlecitinib 200 mg + 50 mg 组的 124 名患者中有 38 名患者（31%），200 mg + 30 mg 组的 121 名患者中有 27 名患者（22%），50 mg 组的 124 名患者中有 29 名患者（23%）。 mg 组、30 mg 组 119 名患者中有 17 名 (14%) 以及安慰剂组 130 名患者中有 2 名 (2%) 根据 SALT 评分 20 或更低有缓解。安慰剂组和 Ritlecitinib 200 mg + 50 mg 组之间基于 SALT 评分 20 或更低的缓解率差异为 29·1% (95% CI 21·2–37·9；p<0·0001)、20· 200 mg + 30 mg 组为 8% (13·7–29·2; p<0·0001)，50 mg 组为 21·9% (14·7–30·2; p<0·0001) ，30 mg 组为 12·8% (6·7–20·4；p=0·0002)。截至第 48 周（包括随访期），ritlecitinib 200 mg + 50 mg 组的 131 名患者中有 108 名患者（82%）报告了 AE。200 mg + 30 mg 组 129 例患者中 105 例（81%），50 mg 组 130 例患者中 110 例（85%），30 mg 组 132 例患者中 106 例（80%），47 例（76%） 10 mg 组的 62 名患者中，65 名患者中的 54 名患者（83%）在延长期内接受了 Ritlecitinib 200 mg + 50 mg 的安慰剂治疗，66 名患者中的 57 名患者（86%）接受了 50 mg 安慰剂组的治疗。各组之间每种 AE 的发生率相似，并且没有死亡病例。Ritlecitinib 对 12 岁及以上斑秃患者有效且耐受性良好。对于适合全身治疗的患者，Ritlecitinib 可能是斑秃的合适治疗选择。辉瑞。